Evaluation of Epigallocatechin-3-Gallate as a Radioprotective Agent During Radiotherapy of Lung Cancer Patients: A 5-Year Survival Analysis of a Phase 2 Study

BackgroundPrevious analysis of the study (NCT02577393) had demonstrated the application of epigallocatechin-3-gallate (EGCG) could be safe and effective in the prevention and treatment of acute radiation esophagitis in patients with advanced lung cancer. EGCG seemed to improve the response rate of small cell lung cancer (SCLC) to radiotherapy in a subgroup analysis. This research continued to analyze the impact of EGCG application on cancer-radiation efficacy and patient survival.MethodsAll patients with SCLC in the NCT02577393 study were included. Patients were randomized into EGCG group or conventional therapy group as protocol. The primary endpoints of the study were radiation response rate and progression-free survival (PFS). Overall survival (OS) and the efficacy of EGCG in the treatment of esophagitis were assessed as secondary endpoints.ResultsA total of 83 patients with lung cancer in the NCT02577393 study were screened, and all 38 patients with SCLC were eligible for analysis. No significant differences with regard to baseline demographic and clinical characteristics were observed between the two groups. The objective response rate (ORR) was higher than that of conventionally treated patients (84.6 vs 50%, P = 0.045), while the median PFS and OS were not significantly prolonged. At data cut-off (1 January 2021), 5-year PFS was 33% with EGCG versus 9.3% with conventional treatment, and 5-year OS was 30.3% versus 33.3%, respectively. The mean adjusted esophagitis index and pain index of patients with EGCG application were lower than conventional treatment (5.15 ± 2.75 vs 7.17 ± 1.99, P = 0.030; 8.62 ± 5.04 vs 15.42 ± 5.04, P < 0.001).ConclusionThe study indicates EGCG may alleviate some esophagitis-related indexes in SCLC patients exposed to ionizing radiation without reducing survival. However, this conclusion should be confirmed by further studies with large sample size

Predictive value of Clinical Frailty Scale in long term prognosis of patients with acute myocardial infarction after in-hospital cardiac rehabilitation

Objective·To investigate the predictive value of the Clinical Frailty Scale (CFS) in the long term outcomes in acute myocardial infarction (AMI) patients who completed in-hospital cardiac rehabilitation (CR).Methods·A total of 501 AMI patients treated in the Cardiology Center of Shanghai Sixth People's Hospital, Shanghai Jiao Tong University of Medicine from May 2020 to May 2022 were prospectively enrolled, with their baseline clinical data collected. The patients completed graded in-hospital CR and were assessed by CFS based on their completion of CR before discharge. Patients were then categorized into three groups (norm group, vulnerable group and frail group) according to their CFS level. The difference in 1-year major cardiovascular event (all-cause death and re-hospitalization for heart failure) rates among the three groups was investigated. Logistic regression analysis was performed to explore the effective risk factors relevant to the outcomes, and receiver operator characteristic (ROC) curves were generated to analyze the prognostic value. Finally, an optimal prediction model was developed.Results·The CFS level in AMI patients who completed CR was positively correlated with age and peak pro-B-type natriuretic peptide (peak proBNP), and inversely correlated with gender difference (P<0.05). Accompanied with the elevated CFS level, the incidence of both outcomes increased, and there were significant differences in all-cause death (2.6%, 5.6% and 15.2%, P=0.002), and while no significant differences in re-hospitalization for heart failure among the three groups (19.6%, 22.2% and 24.2%). All-cause death of the frail group was significantly higher than that of the norm group (P=0.004), while there was no significant difference between the vulnerable group and the norm group. CFS could sensitively predict the 1-year all-cause death in AMI patients (β=1.89, OR=6.61, P=0.001), and the risk model combined with CFS had the best predictive effect (AUC=0.845, P=0.000).Conclusion·Assessment by CFS in AMI patients who completed in-hospital CR contributes to identifying AMI patients with high risk of all-cause death in 1 year

A novel method for in vivo measurement of dynamic ischiofemoral space based on MRI and motion capture

Purpose: To use a novel in vivo method to simulate a moving hip model. Then, measure the dynamic bone-to-bone distance, and analyze the ischiofemoral space (IFS) of patients diagnosed with ischiofemoral impingement syndrome (IFI) during dynamic activities.Methods: Nine healthy subjects and 9 patients with IFI were recruited to collect MRI images and motion capture data. The motion trail of the hip during motion capture was matched to a personalized 3D hip model reconstructed from MRI images to get a dynamic bone model. This personalized dynamic in vivo method was then used to simulate the bone motion in dynamic activities. Validation was conducted on a 3D-printed sphere by comparing the calculated data using this novel method with the actual measured moving data using motion capture. Moreover, the novel method was used to analyze the in vivo dynamic IFS between healthy subjects and IFI patients during normal and long stride walking.Results: The validation results show that the root mean square error (RMSE) of slide and rotation was 1.42 mm/1.84° and 1.58 mm/2.19°, respectively. During normal walking, the in vivo dynamic IFS was significantly larger in healthy hips (ranged between 15.09 and 50.24 mm) compared with affected hips (between 10.16 and 39.74 mm) in 40.27%–83.81% of the gait cycle (p = 0.027). During long stride walking, the in vivo dynamic IFS was also significantly larger in healthy hips (ranged between 13.02 and 51.99 mm) than affected hips (between 9.63 and 44.22 mm) in 0%–5.85% of the gait cycle (p = 0.049). Additionally, the IFS of normal walking was significantly smaller than long stride walking during 0%–14.05% and 85.07%–100% of the gait cycle (p = 0.033, 0.033) in healthy hips. However, there was no difference between the two methods of walking among the patients.Conclusions: This study established a novel in vivo method to measure the dynamic bone-to-bone distance and was well validated. This method was used to measure the IFS of patients diagnosed with IFI, and the results showed that the IFS of patients is smaller compared with healthy subjects, whether in normal or long stride walking. Meanwhile, IFI eliminated the difference between normal and long stride walking

Protection Evaluation of a Five-Gene-Deleted African Swine Fever Virus Vaccine Candidate Against Homologous Challenge

African swine fever virus (ASFV) represents a serious threat to the global swine industry, and there are no safe or commercially available vaccines. Previous studies have demonstrated that inactivated vaccines do not provide sufficient protection against ASFV and that attenuated vaccines are effective, but raise safety concerns. Here, we first constructed a deletion mutant in which EP153R and EP402R gene clusters were knocked out. Based on the deletion mutant, a further deletion from the MGF_360-12L, MGF_360-13L to MGF_360-14L genes was obtained. The five-genes knockout virus was designated as ASFV-ΔECM3. To investigate the efficacy and safety of the ASFV-ΔECM3 virus as a vaccine candidate, the evaluation of the virus was subsequently carried out in pigs. The results showed that the ASFV-ΔECM3 virus could induce homologous protection against the parental isolate, and no significant clinical signs or viremia were observed. These results show that the contiguous deletion mutant, ASFV-ΔECM3 encompassing the EP153R/EP402R and MGF_360-12L/13L/14L genes, could be a potential live-attenuated vaccine candidate for the prevention of ASFV infection

Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway

The aryl hydrocarbon receptor (AhR) is an important immune regulator with a role in inflammatory response. However, the role of AhR in IL-10 production by inflammatory macrophages is currently unknown. In this study, we investigated LPS-induced IL-10 expression in macrophages from AhR-KO mice and AhR-overexpressing RAW264.7 cells. AhR was highly expressed after LPS stimulation through NF-κB pathway. Loss of AhR resulted in reduced IL-10 expression in LPS-induced macrophages. Moreover, the IL-10 expression was elevated in LPS-induced AhR-overexpressing RAW264.7 cells. Maximal IL-10 expression was dependent on an AhR non-genomic pathway closely related to Src and STAT3. Furthermore, AhR-associated Src activity was responsible for tyrosine phosphorylation of STAT3 and IL-10 expression by inflammatory macrophages. Adoptive transfer of AhR-expressing macrophages protected mice against LPS-induced peritonitis associated with high IL-10 production. In conclusion, we identified the AhR-Src-STAT3-IL-10 signaling pathway as a critical pathway in the immune regulation of inflammatory macrophages, It suggests that AhR may be a potential therapeutic target in immune response